title: Discovery of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-ones as novel EGFR inhibitor by scaffold hopping.
abstract: 2-Aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one has been proposed as a novel scaffold of EGFR inhibitor based on scaffold hoping. In the present study, a series of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one derivatives were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against two human cancer cell lines, including A431 and A549. The SAR of the title compounds was preliminarily discussed. The compounds with ideal inhibition were evaluated through ELISA-based EGFR-TK assay. Compound 6c showed the best activity against A431 and EGFR tyrosine kinase. These findings suggest that title compounds are EGFR inhibitors with novel structures.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Bo-Rui
authors.initials: BR
authors.lastname: Kang
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Shan
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: She-Min
authors.initials: SM
authors.lastname: Lu
authors.forename: San-Qi
authors.initials: SQ
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: 2-Arylisoquinolin-1(2H)-ones; Antiproliferative activity; EGFR inhibitor; Scaffold hoping; Synthesis